Imperial College London

Nick S Jones

Faculty of Natural SciencesDepartment of Mathematics

Professor of Mathematical Sciences
 
 
 
//

Contact

 

+44 (0)20 7594 1146nick.jones

 
 
//

Location

 

301aSir Ernst Chain BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Wei:2018:10.1038/s41436-018-0274-3,
author = {Wei, W and Keogh, MJ and Aryaman, J and Golder, Z and Kullar, PJ and Wilson, I and Talbot, K and Turner, MR and McKenzie, C-A and Troakes, C and Attems, J and Smith, C and Sarraj, SA and Morris, CM and Ansorge, O and Jones, NS and Ironside, JW and Chinnery, PF},
doi = {10.1038/s41436-018-0274-3},
journal = {Genetics in Medicine},
pages = {904--912},
title = {Frequency and signature of somatic variants in 1461 human brain exomes},
url = {http://dx.doi.org/10.1038/s41436-018-0274-3},
volume = {21},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - PURPOSE: To systematically study somatic variants arising during development in the human brain across a spectrum of neurodegenerative disorders. METHODS: In this study we developed a pipeline to identify somatic variants from exome sequencing data in 1461 diseased and control human brains. Eighty-eight percent of the DNA samples were extracted from the cerebellum. Identified somatic variants were validated by targeted amplicon sequencing and/or PyroMark® Q24. RESULTS: We observed somatic coding variants present in >10% of sampled cells in at least 1% of brains. The mutational signature of the detected variants showed a predominance of C>T variants most consistent with arising from DNA mismatch repair, occurred frequently in genes that are highly expressed within the central nervous system, and with a minimum somatic mutation rate of 4.25 × 10-10 per base pair per individual. CONCLUSION: These findings provide proof-of-principle that deleterious somatic variants can affect sizeable brain regions in at least 1% of the population, and thus have the potential to contribute to the pathogenesis of common neurodegenerative diseases.
AU - Wei,W
AU - Keogh,MJ
AU - Aryaman,J
AU - Golder,Z
AU - Kullar,PJ
AU - Wilson,I
AU - Talbot,K
AU - Turner,MR
AU - McKenzie,C-A
AU - Troakes,C
AU - Attems,J
AU - Smith,C
AU - Sarraj,SA
AU - Morris,CM
AU - Ansorge,O
AU - Jones,NS
AU - Ironside,JW
AU - Chinnery,PF
DO - 10.1038/s41436-018-0274-3
EP - 912
PY - 2018///
SN - 1098-3600
SP - 904
TI - Frequency and signature of somatic variants in 1461 human brain exomes
T2 - Genetics in Medicine
UR - http://dx.doi.org/10.1038/s41436-018-0274-3
UR - https://www.ncbi.nlm.nih.gov/pubmed/30214067
UR - http://hdl.handle.net/10044/1/65017
VL - 21
ER -